Immune responses to O-specific polysaccharide (OSP) in North American adults infected with Vibrio cholerae O1 Inaba

Abstract

BackgroundAntibodies targeting O-specific polysaccharide (OSP) of Vibrio cholerae may protect against cholera; however, little is known about this immune response in infected immunologically naïve humans.MethodologyWe measured serum anti-OSP antibodies in adult North American volunteers experimentally infected with V. cholerae O1 Inaba El Tor N16961. We also measured vibriocidal and anti-cholera toxin B subunit (CtxB) antibodies and compared responses to those in matched cholera patients in Dhaka, Bangladesh, an area endemic for cholera.Principal findingsWe found prominent anti-OSP antibody responses following initial cholera infection: these responses were largely IgM and IgA, and highest to infecting serotype with significant cross-serotype reactivity. The anti-OSP responses peaked 10 days after infection and remained elevated over baseline for ≥ 6 months, correlated with vibriocidal responses, and may have been blunted in blood group O individuals (IgA anti-OSP). We found significant differences in immune responses between naïve and endemic zone cohorts, presumably reflecting previous exposure in the latter.ConclusionsOur results define immune responses to O-specific polysaccharide in immunologically naive humans with cholera, find that they are largely IgM and IgA, may be blunted in blood group O individuals, and differ in a number of significant ways from responses in previously humans. These differences may explain in part varying degrees of protective efficacy afforded by cholera vaccination between these two populations.Trial registration numberClinicalTrials.gov NCT01895855.

Immune responses to cholera following natural infection: a review

“…In the studies of Harris et al (22) and Alam et al (30), vibriocidal antibody titers were significantly higher from baseline starting at ten days and up to nine months, but had returned to baseline by one year. A return to baseline vibriocidal antibody titers was observed even earlier in three studies, by three (25,32) and six months (36) after acute infection. Four studies had shorter follow-ups, lasting three (33,34) and six (25,32) months.…”

“…A return to baseline vibriocidal antibody titers was observed even earlier in three studies, by three (25,32) and six months (36) after acute infection. Four studies had shorter follow-ups, lasting three (33,34) and six (25,32) months. For these studies, the vibriocidal antibody titers remained significantly different from baseline for the entire duration of the studies.…”

“…The study populations of several studies are notable. First, one study (32) compared the immune responses of two groups, cholera patients in Bangladesh and volunteers in North America. Second, one study included a group of North Americans who had naturally acquired cholera from contaminated food (37) (as opposed to being experimentally infected).…”

“…In our analysis, we identified 13 persistence studies in which sera were collected and measured from residents in Bangladesh (10) (22,25,26,(30)(31)(32)(33)(34)(35)(36), North America (3) (20,32,37), and an unspecified area (assumed India; 1) (38). The study populations of several studies are notable.…”

“…presents seven studies measuring serum vibriocidal antibody responses after infection with V. cholerae(22,25,30,(32)(33)(34)36), all expressed as geometric mean titers. Serological responses at later follow-up days (circles) were compared to the baseline using statistical evidence of significant difference as reflected in the P-value.…”